Chromosome banding analysis of 97 short-term cultured primary breast carcinomas revealed clonal aberrations in 79 tumors, whereas 18 were karyotypically normal. In 34 of the 79 tumors with abnormalities, two to eight clones per case were detected; unrelated clones were present in 27 (34%) cases, whereas only related clones were found in seven. These findings indicate that a substantial proportion of breast carcinomas are of polyclonal origin. Altogether eight abnormalities were repeatedly identified both as sole chromosomal anomalies and as part of more complex karyotypes: the structural rearrangements i(1)(q10), der(1:16)(q10;p10), del(1)(q11-12), del(3)(p12-13p14-21), and del(6)(q21-22) and the numerical aberrations +7, +18, and +20. At least one of these changes was found in 41 (52%) of the karyotypically abnormal tumors. They identify a minimum number of cytogenetic subgroups in breast cancer and are likely to represent primary chromosome anomalies in this type of neoplasia. Other candidates for such a role are translocations of 3p12-13 and 4q21 with various partner chromosomes and inversions of chromosome 7, which also were seen repeatedly. Additional chromosomal aberrations that give the impression of occurring nonrandomly in breast carcinomas include structural rearrangements leading to partial monosomies for 1p, 8p, 11p, 11q, 15p, 17p, 19p, and 19q and losses of one copy of chromosomes X, 8, 9, 13, 14, 17, and 22. The latter changes were seen consistently only in complex karyotypes, however, and we therefore interpret them as being secondary anomalies acquired during clonal evolution.

Cytogenetic analysis of short-term cultures from 52 primary colorectal adenocarcinomas revealed clonal chromosome aberrations in 45 tumors, whereas the remaining 7 had a normal karyotype. More than 1 abnormal clone was detected in 26 tumors; in 18 of them, the clones were cytogenetically unrelated. The modal chromosome number was near-diploid in 32 tumors and near-triploid to near-tetraploid in 13. Only numerical aberrations were identified in 13 carcinomas, only structural aberrations in 3, and 29 had both numerical and structural changes. The most common numerical abnormalities were, in order of decreasing frequency, gains of chromosomes 7, 13, 20, and Y and losses of chromosomes 18, Y, 14, and 15. The structural changes most often affected chromosomes 1, 17, 8, 7, and 13. The most frequently rearranged chromosome bands were, in order of decreasing frequency, 13q10, 17p10, 1p22, 8q10, 17p11, 7q11, 1p33, 7p22, 7q32, 12q24, 16p13, and 19p13. Frequently recurring aberrations affecting these bands were del(1)(p22), i(8)(q10), i(13)(q10), and add(17)(p11-13). The most common partial gains were from chromosome arms 8q, 13q, and 17q and the most common partial losses from chromosome arms 1p, 8p, 13p, and 17p. A correlation analysis between the karyotype and the clinicopathologic features in our total material, which consists of altogether 153 colorectal carcinomas, including 116 with an abnormal karyotype, showed a statistically significant association (P < 0.05) between the karyotype and tumor grade and site. Carcinomas with structural chromosome rearrangements were often poorly differentiated; well and moderately differentiated tumors often had only numerical aberrations or normal karyotypes. Abnormal karyotypes were more common in rectal carcinomas than in carcinomas situated higher up. Near-triploid to near-tetraploid karyotypes were more than twice as frequent in tumors of the distal colon as in those of the proximal colon and rectum. The cytogenetic data indicate that carcinomas located in the proximal colon and rectum, which often are near-diploid with simple numerical changes and cytogenetically unrelated clones, probably arise through different mechanisms than do tumors located in the distal colon, which more often have complex near-triploid to near-tetraploid karyotypes.

The oncofetal CRD-BP/IMP1 RNA binding protein regulates posttranscriptionally a handful of RNA transcripts, implicated in cell adhesion and invadopodia formation and was recently identified as a target of the b-catenin/Tcf transcription factor that is constitutively activated in colorectal carcinomas (CRCs). The expression of CRD-BP/IMP1 was studied in normal adult intestines and CRCs. In normal mucosa, CRD-BP/IMP1 immunoreactivity was observed in few scattered cells located predominantly at or near the bottom of the crypts, whereas in CRCs the protein was detectable in tumor cells of 50% of the specimens analyzed. CRD-BP/ IMP1 mRNA expression was measured by qRT-PCR in 78 CRCs. Thirty-two (41%) of the specimens were negative or had negligible expression, whereas the remaining forty-six (59%) expressed a wide range of CRD-BP/IMP1 mRNA levels. CRD-BP/IMP1 mRNA expression correlated with that of the putative stem/progenitor cell marker Musashi-1 mRNA (p 5 0. 035). CRD-BP/IMP1 positive tumors metastasized and/or recurred more frequently (p 5 0.001) and its expression defined a group of patients with shorter survival (p 5 0.014). Furthermore, in a multivariate analysis CRD-BP/IMP1 expression was found to be an independent predictor of survival (p 5 0.015). For stage I & II patients, the differences in metastasis/recurrence and survival rates remained significant (p 5 0.001 and 0.033, respectively). These findings indicate that CRD-BP/IMP1 positive tumors exhibit early disease dissemination and unfavorable prognosis. ' 2007 Wiley-Liss, Inc.